The development of biodegradable nanocarriers has long been a priority for researchers and medical professionals in the realm of drug delivery. Because of their inherent benefits, which include superior biocompatibility, customizable degradability, easy surface functionalization, and stealth-like behavior, polylactic acid-hyperbranched polyglycerol (PLA-HPG) copolymers have demonstrated a promising future in the field of biomedical research. The synthesis of PLA-HPG copolymers and the creation of their nanoparticles for biomedical uses have been the focus of current efforts. In this review, we summarize the synthetic strategies of PLA-HPG copolymers and corresponding nanoparticles, and highlight their physicochemical properties, biocompatibility, and degradation properties. Furthermore, we introduce a number of PLA-HPG nanoparticles that are utilized for surface skin delivery, wound dressing, and in vivo drug delivery biological applications. Finally, we conclude by offering our thoughts on how this nanoplatform might advance in the future.